This project has three major goals: 1. The isolation and characterization of the somatomedins present in rat serum. Isolation procedures have been developed which have resulted in the partial characterization of a basic peptide which is bound by somatomedin receptors and is biologically active on cartilage from hypophysectomized rats in vitro. With additional fractionation we should achieve a preparation of sufficient purity for sequence analysis in collaboration with Dr. Ralph Bradshaw. This preparation will be used for radioimmunoassay studies and comparative binding studies with MSA and other somatomedin peptides. 2. The second major goal of this laboratory is to characterize the mechanism of defective growth of children with extreme proportionate slowing of growth who have normal to increased concentration of RIA measurable GH. We will characterize the circulating GH in terms of its radioreceptor activity with IM-9 lymphocytes. The level of somatomedin will be measured by rat cartilage bioassay and 125I-IGF-I radioreceptor assay. The growth characteristics of fibroblasts isolated from these children will be compared to fibroblasts from children with normal growth in response to known quantities of purified MSA or somatomedin. 3. We have developed a relatively specific radioreceptor assay for IGF-II in plasma. Our initial studies with this method indicate that the level of this growth peptide is independently controlled. The possible significance of IGF-II in fetal growth and hypoglycemic states is under study.